ABSTRACT This proposal addresses the clinical deficiency of the currently available oral treatments for hypothyroidism. Whereas levothyroxine (LT4, Synthroid and other products) is the standard of care and effectively resolves symptoms in most patients, some hypothyroid patients are commonly treated with a combination of LT4 and liothyronine (LT3, Cytomel and other products). LT3 has the disadvantage of being absorbed too rapidly, too short-lived and associated with potential side-effects to act as an effective complement to T4. If the value of combining T3 with T4 is to be ultimately realized for these patients, a controlled release product that delivers T3 in a fashion that produces physiologically normal (euthyroid) plasma levels will be needed. Euthyroid plasma T3 levels are important to achieve normal thyroid hormone concentrations in all tissues. The broad, long- term objective of this product is to provide patients a new thyroid hormone drug product that produces euthyroid-like T3 levels with once daily oral dosing. The metallo-T3 complexes are designed to be insoluble. They slowly pass through and settle in the gastrointestinal tract where T3 molecules gradually break free from the metal complex and enter the blood stream. This modulates the rate of delivery and thereby the rate of T3 drug absorption.